CRISPR-Cas9 Mediated Gene Editing and its Impact on Cancer Immunotherapy

Gemma Forner^*
*Correspondence: Gemma Forner, Department of Medicine, University of Montreal, Montreal, QC H3C 3J7, Canada, Email:

Keywords

CRISPR-Cas9 • Gene editing • Cancer immunotherapy • Oncogenes

Introduction

Cancer remains one of the leading causes of mortality worldwide, with traditional treatments often limited by resistance and toxicity. Immunotherapy has emerged as a groundbreaking approach, harnessing the body's immune system to target and eliminate cancer cells. However, the efficacy of immunotherapy can be hindered by various genetic and molecular factors within tumors and the immune system itself. The advent of CRISPR-Cas9 technology has provided a powerful tool for precise genetic modifications, offering new avenues to enhance the effectiveness of cancer immunotherapy. This paper aims to review the current state of CRISPR-Cas9 applications in cancer immunotherapy, highlighting key advancements and potential future directions [1].

Literature Review

CRISPR-Cas9 technology is revolutionizing cancer immunotherapy through its ability to make precise genetic alterations that enhance immune cell functions and target cancer-specific genetic elements. One of the primary uses of CRISPR-Cas9 in cancer therapy is to modify T cells, key players in the immune response. By knocking out inhibitory receptors such as PD-1 and CTLA-4, CRISPR can prevent these receptors from dampening the immune response. PD-1 and CTLA-4 are checkpoints that tumors exploit to evade the immune system. By removing these checkpoints, T cells can maintain their activity against cancer cells, leading to a more robust anti-tumor response. Another exciting application is the engineering of CAR T cells. These are T cells that have been modified to express chimeric antigen receptors that recognize specific proteins on cancer cells. CRISPR-Cas9 can enhance the precision and efficiency of these modifications, improving the ability of CAR T cells to target and destroy cancer cells while minimizing damage to healthy cells [2].

CRISPR-Cas9 also plays a crucial role in targeting oncogenes and tumor suppressors. Oncogenes are mutated genes that drive the uncontrolled growth and spread of cancer cells. CRISPR-Cas9 can be used to specifically target and knock out these oncogenes, thereby inhibiting cancer progression. Conversely, tumor suppressor genes, when functioning correctly, can prevent cancer formation. Mutations often deactivate these genes in cancer cells. CRISPR-Cas9 can be employed to repair these mutations, reactivating the tumor suppressor genes and restoring their protective effects [3]. Another significant application of CRISPR-Cas9 in cancer therapy is overcoming resistance mechanisms. Cancer cells frequently develop resistance to conventional therapies through genetic mutations. CRISPR-Cas9 can identify and correct these mutations, thereby resensitizing cancer cells to treatments. For instance, if a mutation renders a cancer cell resistant to a particular drug, CRISPR can be used to correct that mutation, restoring the cell's sensitivity to the drug. This capability addresses one of the major hurdles in effective cancer treatment, making it possible to extend the efficacy of existing therapies [4].

Despite its transformative potential, CRISPR-Cas9 faces several challenges. One of the significant concerns is its potential to cause off-target effects, where the CRISPR machinery edits unintended parts of the genome. These off-target modifications can lead to unintended consequences, including the possibility of new mutations that could drive cancer or other diseases. Additionally, the ability to edit human genes raises various ethical questions. Concerns include the long-term effects of genetic modifications, potential misuse of the technology, and the moral implications of making heritable changes to the human genome. Given its profound implications, CRISPR-Cas9 technology is subject to rigorous regulatory scrutiny. Ensuring the safety, efficacy, and ethical use of CRISPR-based therapies involves navigating complex regulatory landscapes, which can slow the development and implementation of these promising treatments [5].

Discussion

The application of CRISPR-Cas9 in cancer immunotherapy has shown significant promise in preclinical and clinical studies. By enabling precise modifications of immune cells and tumor-related genes, researchers can design more effective and personalized therapeutic strategies. However, challenges such as off-target effects, ethical considerations, and the complexity of tumor microenvironments must be addressed to fully realize the potential of CRISPR-Cas9. Ongoing advancements in gene-editing techniques, combined with a deeper understanding of tumor biology and immune interactions, will be crucial for overcoming these obstacles [6].

Conclusion

CRISPR-Cas9 mediated gene editing represents a transformative approach in the field of cancer immunotherapy. Its ability to enhance immune cell functions, target oncogenes, and overcome resistance mechanisms provides a promising pathway for developing next-generation cancer treatments. While challenges remain, continued research and technological improvements are likely to expand the applicability and efficacy of CRISPRCas9 in oncology. The future of cancer immunotherapy lies in the integration of precise genetic editing with advanced immunological strategies, paving the way for more effective and personalized interventions against cancer.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Valle, Juan W., R. Katie Kelley, Bruno Nervi and Do-Youn Oh, et al. "Biliary tract cancer." The Lancet 397 (2021): 428-444.

   Google Scholar, Crossref, Indexed at

2. Brindley, Paul J., Melinda Bachini, Sumera I. Ilyas and Shahid A. Khan, et al. "Cholangiocarcinoma." Nat Rev Dis Primers 7 (2021): 65.

   Google Scholar, Crossref, Indexed at

3. Ilyas, Sumera I., Silvia Affo, Lipika Goyal and Angela Lamarca, et al. "Cholangiocarcinoma—novel biological insights and therapeutic strategies." Nat Rev Clin Oncol 20 (2023): 470-486.

   Google Scholar, Crossref, Indexed at

4. Valle, Juan, Harpreet Wasan, Daniel H. Palmer and David Cunningham, et al. "Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer." N Engl J Med 362 (2010): 1273-1281.

   Google Scholar, Crossref, Indexed at

5. Valle, Juan W., J. Furuse, M. Jitlal, S. Beare and N. Mizuno, et al. "Cisplatin and gemcitabine for advanced biliary tract cancer: A meta-analysis of two randomised trials." Ann Oncol 25 (2014): 391-398.

   Google Scholar, Crossref, Indexed at

6. Oh, Do-Youn, Aiwu Ruth He, Shukui Qin and Li-Tzong Chen, et al. "Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer." NEJM Evidence 1 (2022): EVIDoa2200015.

   Google Scholar, Crossref, Indexed at